OBJECTIVE: The objective of the study was to investigate the transgenerational effect of fetal vascular programming STUDY DESIGN: Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO-/-) mothers lacking a functional NOS3 (KOM) vs wild-type control mothers (KOP). The first-generation KOM(+/-) and KOP(+/-) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in vitro vascular reactivity studies. RESULTS: WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic blood pressure, mean arterial pressure, and pulse pressure, compared with WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE), compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared with female. Acetylcholine responses were decreased in female KOM-F2WT, compared with female KOP-F2WT, but the difference was not statistically significant CONCLUSION: Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.
OBJECTIVE: The objective of the study was to investigate the transgenerational effect of fetal vascular programming STUDY DESIGN: Homozygous NOS3 knockout and wild type controls (NOS3+/+WT) were cross-bred to obtain heterozygous offspring that developed in (KO-/-) mothers lacking a functional NOS3 (KOM) vs wild-type control mothers (KOP). The first-generation KOM(+/-) and KOP(+/-) female mice were then bred with WT(+/+) males to obtain a second generation (F2). F2 offspring were genotyped and WT(+/+)-F2 mice were then used for in vivo blood pressure and in vitro vascular reactivity studies. RESULTS: WT-F2 mice born to KOM mothers (KOM-F2WT) had significantly higher systolic blood pressure, mean arterial pressure, and pulse pressure, compared with WT-F2 born to KOP mothers. Male KOM-F2WT offspring had significantly increased response to phenylephrine (PE), compared with male KOP-F2WT. Male offspring had increased contractile responses to PE when compared with female. Acetylcholine responses were decreased in female KOM-F2WT, compared with female KOP-F2WT, but the difference was not statistically significant CONCLUSION: Our findings support a transgenerational effect of fetal programming on the vascular phenotype and suggest possible gender specific adaptation.
Authors: Maged M Costantine; Francesca Ferrari; Giusseppe Chiossi; Esther Tamayo; Gary D V Hankins; George R Saade; Monica Longo Journal: Am J Obstet Gynecol Date: 2009-07-26 Impact factor: 8.661
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Authors: Esther F Davis; Laura Newton; Adam J Lewandowski; Merzaka Lazdam; Brenda A Kelly; Theodosios Kyriakou; Paul Leeson Journal: Clin Sci (Lond) Date: 2012-07 Impact factor: 6.124